Synthesis of the 6-deoxytalose-containing tetrasaccharide of the glycopeptidolipid from Mycobacterium intracellare serotype 7

Article abstract of DOI:10.1016/j.carres.2008.09.010

An efficient synthesis of 4-methoxyphenyl α-l-Rhap-(1→3)-α-l-Rhap-(1→3)-α-l-Rhap-(1→2)-6-deoxy-α-l-Talp, the tetrasaccharide related to the GPLs of Mycobacterium intracellare serotype 7, was achieved with 4-methoxyphenyl 3,4-di-O-benzoyl-6-deoxy-α-l-talop

Full text of DOI:10.1016/j.carres.2008.09.010

Carbohydrate Research 343 (2008) 3107–3111
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Note
Synthesis of the 6-deoxytalose-containing tetrasaccharide of the
glycopeptidolipid from Mycobacterium intracellare serotype 7
a
b
Shiqiang Yan a, Xiaomei Liang a, Peiyu Diao a, Ye. Yang a, Jianjun Zhang a, , Daoquan Wang , Fanzuo Kong
*
a Key Lab of Pesticide Chemistry and Application Technology, Department of Applied Chemistry, China Agricultural University, Beijing 100094, China
b Research Center for Eco-Environmental Sciences, Academia Sinica, PO Box 2871, Beijing 100085, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 10 July 2008
Received in revised form 4 September 2008
Accepted 15 September 2008
Available online 20 September 2008
An efficient synthesis of 4-methoxyphenyl
a
-
L
-Rhap-(1?3)-
a
-
L
-Rhap-(1?3)-
a
-
L
-Rhap-(1?2)-6-deoxy-
a-
L
-Talp, the tetrasaccharide related to the GPLs of Mycobacterium intracellare serotype 7, was achieved
with 4-methoxyphenyl 3,4-di-O-benzoyl-6-deoxy- -talopyranoside (6c) as the key intermediate which
was obtained through selective 3-O-benzoylation of 4-O-benzoyl-6-deoxy- -taloside. Coupling of 6c
with 3-O-allyloxycarbonyl-2,4-di-O-benzoyl- -rhamnopyranosyl trichloroacetimidate followed by
removal of the allyloxycarbonyl protecting group afforded the disaccharide acceptor 11. Condensation
of 11 with 2,3,4-tri-O-benzoyl- -rhamnopyranosyl-(1?3)-2,4-di-O-benzoyl- -rhamnopyranosyl
trichloroacetimidate and subsequent deprotection gave the target tetrasaccharide.
a
-L
a
-L
a
-L
Keywords:
Rhamnose
6-Deoxy-a-L-talose
Tetrasaccharide
a
-
L
a-L
Ó 2008 Elsevier Ltd. All rights reserved.
Selective acylation
6-Deoxy-
L
-talose is a key building block of many biologically
glycos-4-ulose derivative 2 in 93% yield. Reduction of 2 with
sodium borohydride gave 4-methoxyphenyl 6-deoxy-2,3-O-iso-
propylidene-a-L-talopyranoside (3) as crystals in 85% yield. The
important glycopeptidolipids (GPLs)1–4 and is an essential compo-
nent of numerous antigenic bacterial lipopolysaccharides (LPSs)5–9
Structural analysis revealed that most of these GPLs or LPSs possess
Tal-configuration of 3 was assigned from its 1H NMR spectrum,
showing characteristic signals at d 3.63 ppm (dd, J3,4 = J4,5 5.1 Hz)
for H-4.14 Compared to the previously reported synthesis of methyl
or benzyl deoxytalosides,18–20 the main advantage for the synthe-
sis of the pMP glycoside in the present work was that the pMP
taloside could be purified by crystallization, avoiding the tedious
column chromatography purification step. Acylation of 3 with
benzoyl chloride or pivaloyl chloride in pyridine followed by de-
isopropylidenation provided the 2,3-diol 4 (92%) or 5 (76%), respec-
tively. Compounds 4 and 5 were employed for the selective acyla-
tion reactions. Because the equatorially oriented 3-OH is more
reactive than the axial 2-OH, it was anticipated that the 3-OH could
be selectively acylated. As a typical example, 4 was treated with
acetyl chloride in dichloromethane at ꢀ10 °C in the presence of
4 equiv of pyridine and catalytic amounts of DMAP, resulting in
the 3-O-acetyl derivative (6a) in excellent yield (93%). Other acyl-
ation reagents such as allyloxycarbonyl chloride, benzoyl chloride,
chloroacetyl chloride, phenylacetyl chloride, and pivaloyl chloride
were also investigated for the regioselective esterification, and in
all cases the 3-OH acylated products 6b–f and 7a–d were obtained
in high yield (80–95%). Low temperature and slow addition of the
chlorides were necessary for optimal regioselectivity. The
regioselectivity of the process was established by 1H NMR
spectroscopy, and the characteristic H-3 signal was found to move
to downfield upon acylation (dH-3 4.33 ppm in 4 as compared to
dH-3 5.49 ppm in 6a). Further confirmation was supported by the
the 6-deoxy-L-talose unit in which O-2 or O-3 is glycosylated with
other sugar units. Recently, it was proposed that the oligosaccha-
ride part of Mycobacterium intracellare serotype 7 GPLs contains a
pentasaccharide, which is composed of one 6-deoxy-L-talose, three
L-rhamnoses, and one terminal amido sugar unit, while the config-
uration of the terminal amido sugar remained undetermined (I,
Chart 1).10
M. intracellulare is distributed ubiquitously in nature and is an
important cause of respiratory and lymphatic disease in human
and animals.11 Since carbohydrates play an important role in bac-
terial physiology and pathogenesis, preparation of these GPL oligo-
saccharides is of considerable interest for structure–bioactivity
studies of carbohydrates.12–15 In this paper, we wish to report
the efficient synthesis of the well-defined tetrasaccharide II (Chart
1) related to the GPLs of M. intracellare serotype 7.
For the synthesis of the tetrasaccharide, 4-methoxyphenyl 6-
deoxy-
droxyl free were prepared through the regioselective acylation of
6-deoxy- -taloside 2,3-diols (4, or 5) with acyl chlorides. As out-
lined in Scheme 1, 4-methoxyphenyl 2,3-O-isopropylidene-
a-L-talopyranoside acceptors (6a–f, 7a–d) with the C-2 hy-
a-L
a-L-
rhamnopyranoside (1), obtained by a reported method from rham-
nose,16 was oxidized with PDC17 to afford the corresponding
* Corresponding author. Tel.: +86 10 62731115; fax: +86 10 62732219.
E-mail address: zhangjianjun@cau.edu.cn (J. Zhang).
0008-6215/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2008.09.010

3108
S. Yan et al. / Carbohydrate Research 343 (2008) 3107–3111
H
CH3
H
CH2
H
N
O
C
H
N
H3CO
O
C
C
CH3
H
C
N
H
C
O
C
O
C
C
H3C(H2C)11HC HC(H2C)15HCH2C
HN
H
H3C
CH
O
CH2
O
H3C
HO
O
HO
O
O
H3C
OCH3
OCH3
HO
O
HO
O
H3C
HO
CH3
O
I
HO
O
H3C
HO
HO
O
H3C
HO
O
O
H3C
HO
H3C
O
HO
HO
O
H3C
O
HO
H3C
HO
HO
O
OPMP
OCH3
C
O
H3C
CH
OH
HO
O
O
O
N
H
HO
HO
HO
II
Chart 1. Proposed structure of the M. intracellare serotype 7 GPL I and the target tetrasaccharide II.
OPMP
Me
OPMP
OPMP
OPMP
Me
O
Me
HO
O
O
Me
O
c
a
b
O
O
O
O
HO
O
O
C
OH
O
OR
OH
C
C
Me2
Me2
Me2
4 R = Bz
1
2
3
5 R = Piv
6a R = Ac (93%)
6b R = Alloc (85%)
PMPO
PMPO
7a R = Ac (85%)
7b R = Alloc (81%)
7c R = Bz (92%)
7d R = Piv (71%)
6c R = Bz
(95%)
Me
O
Me
O
d
d
4
5
6d R = CA (88%)
6e R = BnCO (90%)
6f R = Piv (80%)
RO
OBz
RO
OPiv
OH
OH
Scheme 1. Reagents and conditions: (a) PDC, CH2Cl2, reflux, 6–8 h, 93%; (b) EtOAc–water (7:3), NaBH4, 85%; (c) (i) BzCl or PivCl, pyridine, cat DMAP, rt, 2 h; (ii) 70% AcOH,
75 °C, 2 h, 92% for 4; 76% for 5; (d) acyl chloride–pyridine, cat DMAP, CH2Cl2, rt.
single-crystal X-ray analysis of 4-methoxyphenyl 3-O-allyloxycar-
bonyl-2,4-di-O-benzoyl-6-deoxy- -talopyranoside (14), ob-
tained from benzoylation of compound 6b (preparation of 14 and
H-1 of a-Tal along with three doublets at d 5.29 ppm (J 1.8 Hz), d
a
-L
4.84 ppm (J 1.2 Hz), and d 4.69 ppm (J 0.6 Hz) for the three a-Rha
anomeric protons, respectively. The 13C NMR spectrum showed
peaks at d 99.8, 99.0, 99.0, and 98.6 for the four anomeric carbons.
Finally deacylation of 13 in ammonium-saturated methanol gave
the target tetrasaccharide II (Chart 1).
its X-ray data are included in the Supplementary data).
With the 6-deoxytaloside acceptors possessing a free 2-OH at
hand, synthesis of the target tetrasaccharide was readily achieved
as shown in Scheme 2. In the synthesis, 4-methoxyphenyl 3-O-
In conclusion, we have explored the highly selective acylation at
allyloxycarbonyl-2,4-di-O-benzoyl-
the disaccharide donor 2,3,4-tri-O-benzoyl-
(1?3)-2,4-di-O-benzoyl- -rhamnopyranosyl trichloroacetimi-
date (12) were prepared from -rhamnose according to the previ-
a
-
L
-rhamnopyranoside (8) and
O-3 of 6-deoxy-
dine as mild esterification reagents, and a 6-deoxy-a-L
nose-containing tetrasaccharide from the GPLs of M. intracellare
serotype 7 was efficiently synthesized.
a
-
L
-taloside 2,3-diols with acyl chloride and pyri-
a
-L
-rhamnopyranosyl-
-talopyra-
a-
L
L
ously reported procedures.21,22 Cleavage of the 4-methoxyphenyl
group of 8 with ceric ammonium nitrate (CAN), followed by tri-
chloroacetimidation, provided 9. Then, condensation of the donor
1. Experimental
9 with 4-methoxyphenyl 3,4-di-O-benzoyl-6-deoxy-a-L-talopyr-
1.1. General methods
anoside (6c) in the presence of TMSOTf23 afforded the disaccharide
10, and subsequent de-allyloxycarbonylation of 10 with palladium
catalyst (Pd[P(C6H5)3]4, 0.05 equiv), P(C6H5)3 (0.3 equiv), and Et3N
(2 equiv) in THF24 gave the disaccharide acceptor 11 in satisfactory
yield. TMSOTf-catalyzed coupling reaction of the acceptor 11 with
the donor 12 provided the tetrasaccharide 13 in 76% yield. The 1H
NMR spectrum of 13 showed a doublet at d 5.75 ppm (J 1.2 Hz) for
Optical rotations were determined with a Perkin–Elmer model
241-MC automatic polarimeter for solns in a 1-dm jacketed cell.
1H and 13C NMR spectra were recorded with Bruker DPX300 and
Bruker AVANCE600 spectrometers in CDCl3 or D2O solns. Internal
references: TMS (d 0.000 ppm for 1H), CDCl3 (d 77.00 ppm for
13C), and HOD (d 4.700 for 1H). 1H NMR signals of some compounds

S. Yan et al. / Carbohydrate Research 343 (2008) 3107–3111
3109
OPMP
Me
O
OCNHCCl3
BzO
OPMP
O
OBz
b, 6c
a
Me
BzO
AllocO
Me
BzO
AllocO
O
O
Me
BzO
O
OBz
OBz
AllocO
8
OBz
Me
9
10
OPMP
OPMP
OPMP
Me
O
O
O
Me
c
BzO
OBz
O
BzO
OBz
O
11
HO
O
O
OH
Me
BzO
O
O
Me
BzO
Me
HO
b
HO
d
OBz
O
O
BzO
HO
Cl3CHNCO
O
O
Me
BzO
Me
BzO
Me
HO
O
BzO
O
HO
O
O
OBz
Me
BzO
O
O
O
Me
BzO
Me
HO
BzO
OBz
BzO
BzO
HO
HO
II
13
12
Scheme 2. Reagents and conditions: (a) (i) 80% MeCN, CAN, 35 °C, 0.5 h, 78%; (ii) CCl3CN, DBU, CH2Cl2, rt, 0.5 h, 89%; (b) TMSOTf, CH2Cl2, ꢀ10 °C to rt, 2 h, 88% for 10; 76% for
13; (c) Pd[P(C6H5)3]4, P(C6H5)3, Et3N, THF, rt, 81%; (d) satd NH3–MeOH, rt, 96 h, 91%.
were assigned with the aid of COSY. Elemental analysis was per-
formed on a Yanaco CHN Corder MF-3 automatic elemental ana-
lyzer. MALDI and ESI mass spectra were performed by the
Institute of Chemistry of the Chinese Academy of Sciences. Thin-
layer chromatography (TLC) was performed on Silica Gel HF with
detection by charring with 30% (v/v) H2SO4 in MeOH or by UV
detection. Column chromatography was conducted by elution of
a column of silica gel (200–300 mesh) with EtOAc–petroleum ether
(bp 60–90 °C) as the eluent. Solns were concentrated at a temper-
ature <60 °C under diminished pressure.
at 0 °C for 15 min, and TLC (4:1 petroleum ether–EtOAc) indicated
that the reaction was complete. The aq soln was extracted with
EtOAc (3 ꢂ 200 mL), the extract was washed with M HCl and satd
aq NaHCO3, dried (Na2SO4), and concentrated to give crude 3 as a
syrup. Purification of the crude product by crystallization (4:1
petroleum ether–EtOAc) provided 3 (13.2 g, 85%) as white crystals
(mp 93–94 °C); ½a D25
ꢁ
ꢀ75.0 (c 1.0 CHCl3); 1H NMR (300 MHz,
CDCl3): d 1.29 (d, J5,6 6.6 Hz, 3H, CH3), 1.42, 1.61 (2s, 6H, CMe2),
2.32 (d, 1H, OH, exchangeable with D2O), 3.63 (dd,
J3,4 = J4,5 = 5.1 Hz, 1H, H-4), 3.76 (s, 3H, OMe), 4.00 (m, 1H, H-5),
4.27 (dd, J1,2 0.8 Hz, J2,3 6.4 Hz, 1H, H-2), 4.36 (d, J2,3 6.4 Hz, J3,4
5.1 Hz, 1H, H-3), 5.66 (s, 1H, H-1), 6.84 (m, 2H, Ar-H), 7.00 (m,
2H, Ar-H). Anal. Calcd for C16H22O6: C, 61.92; H, 7.15. Found: C,
62.11; H, 7.02.
1.2. 4-Methoxyphenyl 6-deoxy-2,3-O-isopropylidene-a-L-lyxo-
hexopyranosid-4-ulose (2)
A
mixture of 4-methoxyphenyl 2,3-O-isopropylidene-a-L-
rhamnopyranoside (1)16 (31.0 g, 0.1 mol), PDC (23.0 g, 0.06 mol),
and acetic anhydride (28.4 mL, 0.3 mol) in CH2Cl2 (200 mL) was
stirred at reflux for 8 h, at the end of which time TLC (4:1 petro-
leum ether–EtOAc) indicated that the reaction was complete. After
direct concentration of the reaction mixture, the dark brown resi-
due was diluted with EtOAc (60 mL) and the soln was passed
through a short (5–10 cm) silica-gel column. The column was
eluted with EtOAc and the eluents were concentrated and coevap-
orated with toluene. The residue was subjected to silica-gel col-
umn chromatography again (4:1 petroleum ether–EtOAc) to give
1.4. 4-Methoxyphenyl 4-O-benzoyl-6-deoxy-a-L-talopyranoside
(4)
To a soln of 3 (12.4 g, 0.04 mol) in pyridine (60 mL) was added
benzoyl chloride (5.6 mL, 0.048 mol) dropwise. After stirring for
8 h at rt, TLC (3:1 petroleum ether–EtOAc) indicated that the reac-
tion was complete. MeOH (1 mL) was added to quench the reaction
and then water (100 mL) was added to the reaction mixture. The aq
soln was extracted with EtOAc (3 ꢂ 200 mL), the extract was
washed with M HCl and satd aq sodium hydrogencarbonate, dried
(Na2SO4), and concentrated. The residue was dissolved in 70%
AcOH (200 mL) and stirred for 3 h at 75 °C, at the end of which time
TLC (2:1 petroleum ether–EtOAc) indicated completion of the reac-
tion. The mixture was concentrated under diminished pressure and
then coevaporated with toluene (2 ꢂ 40 mL). The residue was
passed through a short silica-gel column with 5:2 petroleum
ether–EtOAc as the eluent to give 4 (13.8 g, 92% for two steps) as
2 (28.6 g, 93%) as a syrup; ½a D25
ꢁ
ꢀ90.1 (c 0.5 CHCl3); 1H NMR
(300 MHz, CDCl3): d 1.38 (d, J5,6 6.8 Hz, 3H, H-6), 1.41, 1.54 (2s,
6H, CMe2), 3.78 (s, 3H, OMe), 4.30 (q, J5,6 6.8 Hz, 1H, H-5), 4.55–
4.65 (m, 2H, H-2, H-3), 5.59 (s, 1H, H-1), 6.84 (m, 2H, Ar-H), 7.00
(m, 2H, Ar-H). Anal. Calcd for C16H20O6: C, 62.33; H, 6.54. Found:
C, 62.09; H, 6.86.
1.3. 4-Methoxyphenyl 6-deoxy-2,3-O-isopropylidene-
a-
L-
a foamy solid; ½a D25
ꢁ
+48.0 (c 0.5 CHCl3); 1H NMR (600 MHz, CDCl3):
talopyranoside (3)
d 1.22 (d, J5,6 6.6 Hz, 3H, CH3), 2.65 (br s, 2H, 2OH), 3.82 (s, 3H,
OMe), 4.03 (dd, J1,2 1.8 Hz, J2,3 3.6 Hz, 1H, H-2), 4.30 (q, J5,6
6.6 Hz, 1H, H-5), 4.33 (dd, J2,3 = J3,4 = 3.6 Hz, 1H, H-3), 5.53 (d, J3,4
3.6 Hz, 1H, H-4), 5.61 (d, J1,2 1.8 Hz, 1H, H-1), 6.87 (m, 2H, Ar-H),
To a soln of 2 (15.4 g, 0.05 mol) in 7:3 EtOAc–water (150 mL) at
0 °C was added NaBH4 (2.1 g, 0.055 mol). The mixture was stirred

3110
S. Yan et al. / Carbohydrate Research 343 (2008) 3107–3111
7.04 (m, 2H, Ar-H), 7.47–8.08 (m, 5H, Bz-H). Anal. Calcd for
C20H22O7: C, 64.16; H, 5.92. Found: C, 63.90; H, 6.20.
(0.30 mL, 30 mmol) in dry CH2Cl2 (40 mL) was stirred until com-
pletion of the reaction (TLC, 3:1 petroleum ether–EtOAc). Concen-
tration and purification of the residue by flash chromatography
(6:1 petroleum ether–EtOAc) gave 9 (6.26 g, 89%) as a white foamy
1.5. 4-Methoxyphenyl 6-deoxy-4-O-pivaloyl-a-L-talopyranoside
(5)
solid; ½a 2D5
ꢁ
+60.0 (c 1.0 CHCl3); 1H NMR (300 MHz, CDCl3): d 1.39 (d,
J5,6 6.2 Hz, 3H, CH3), 4.30 (m, 1H, H-5), 4.49–4.51 (m, 2H,
OCH2CH@CH2), 5.02–5.18 (m, 2H, OCH2CH@CH2), 5.52–5.72 (m,
3H, OCH2CH@CH2, H-3, H-4), 5.82 (dd, J1,2 2.0 Hz, J2,3 3.2 Hz, 1H,
H-2), 6.44 (d, J1,2 2.0 Hz, H-1), 7.44–7.62 (m, 6H, Ar-H), 8.04–8.14
(m, 4H, Ar-H), 8.81 (s, 1H, CNHCCl3). Anal. Calcd for C26H24Cl3NO9:
C, 51.97; H, 4.03; N, 2.33. Found: C, 51.82; H, 4.34; N, 2.72.
To a soln of 3 (6.2 g, 20 mmol) with DMAP (1.0 g, 8.0 mmol) in
pyridine (30 mL) was added pivaloyl chloride (4.8 mL, 40 mol)
dropwise. After stirring for 2 d at rt, TLC (3:1 petroleum ether–
EtOAc) indicated that the reaction was complete. MeOH (0.5 mL)
was added to the reaction mixture followed by stirring for
10 min. Water (100 mL) was added and the aq soln was extracted
with CH2Cl2 (3 ꢂ 50 mL), the extract was washed with M HCl and
satd aq sodium hydrogencarbonate, dried (Na2SO4), and concen-
trated. The residue was dissolved in 70% AcOH (200 mL) and stirred
for 3 h at 70 °C, at the end of which time TLC (2:1 petroleum ether–
EtOAc) indicated that the reaction was complete. The mixture was
concentrated and coevaporated with toluene (2 ꢂ 40 mL). The res-
idue was passed through a short silica-gel column with 5:2 petro-
leum ether–EtOAc as the eluent to give 5 (5.4 g, 76% for two steps)
1.8. 4-Methoxyphenyl 3-O-allyloxycarbonyl-2,4-di-O-benzoyl-
a-L
-rhamnopyranosyl-(1?2)-3,4-di-O-benzoyl-6-deoxy–
L-
talopyranoside (10)
To a cooled soln (ꢀ10 °C) of 9 (3.99 g, 6.6 mmol) and 6c (2.65 g,
5.5 mmol) in anhyd CH2Cl2 (45 mL) was added TMSOTf (25 L,
l
0.14 mmol). The mixture was stirred at this temperature for 2 h,
and then quenched with Et3N (2 drops). The solvents were evapo-
rated under diminished pressure to give a residue, which was puri-
fied by silica-gel column chromatography (5:1 petroleum ether–
EtOAc) to give disaccharide 10 (4.43 g, 88%) as a foamy solid;
as a foamy solid; ½a D25
ꢁ
+44.5 (c 0.5 CHCl3); 1H NMR (300 MHz,
CDCl3): d 1.13 (d, J5,6 5.0 Hz, 3H, CH3), 1.30 (s, 9H, (CH3)3CCO),
2.56 (d, J 11.3 Hz, 1H, OH), 2.69 (d, J 7.8 Hz, 1H, OH), 3.78 (s, 3H,
OCH3), 3.95 (m, 1H, H-2), 4.15–4.21 (m, 2H, H-3, H-5), 5.25 (d,
J3,4 3.7 Hz, 1H, H-4), 5.58 (d, J1,2 1.5 Hz, 1H, H-1), 6.82–6.86 (m,
2H, Ar-H), 6.96–7.02 (m, 2H, Ar-H). Anal. Calcd for C18H26O7: C,
61.00; H, 7.39. Found: C, 60.86; H, 7.22.
½
a 2D5
ꢁ
ꢀ28.0 (c 1.0 CHCl3); 1H NMR (300 MHz, CDCl3): d 1.26 (d, J
5.6 Hz, 3H, CH3), 1.33 (d, J 5.9 Hz, 3H, CH3), 3.80 (s, 3H, OCH3),
4.23–4.32 (m, 2H), 4.47–4.49 (m, 3H, H-2, OCH2CH@CH2), 5.03–
5.19 (m, 2H, OCH2CH@CH2), 5.26 (s, 1H), 5.50–5.56 (m, 2H),
5.64–5.76 (m, 4H), 5.87 (dd, J2,3 = J3,4 = 3.6 Hz, 1H, H-3), 6.88–6.91
(m, 2H, Ar-H), 7.09–7.12 (m, 2H, Ar-H), 7.31–7.64 (m, 12H, Bz-H),
7.96–8.20 (m, 8H, Bz-H); 13C NMR (300 MHz, CDCl3) d 16.3, 17.6,
55.7, 65.9, 67.6, 67.9, 68.7, 69.2, 70.1, 71.9, 72.4, 72.7, 98.7 (C-1),
99.1 (C-1), 114.8, 117.5, 118.8, 128.4, 128.4, 128.5, 128.6, 129.2,
129.2, 129.3, 129.8, 129.9, 130.1, 131.2, 133.0, 1332, 133.3, 133.5,
150.1, 153.9, 155.2, 164.8, 165.5, 165.6, 166.4. Anal. Calcd for
C51H48O16: C, 66.80; H, 5.28. Found: C, 66.67; H, 5.39.
1.6. General procedure for the preparation of compounds 6a–e
and 7a–d
Compound 4 or 5 (2 mmol), in a 100 mL round-bottomed flask,
was dried under high vacuum for 4 h, and then anhyd CH2Cl2
(20 mL), pyridine (4.0 mL, 50 mmol) and, in the case of 6f and 7d,
catalytic amounts of DMAP (50 mg, 0.4 mmol) were successively
added to the flask under N2 atmosphere. The flask was cooled to
ꢀ15 °C in an ice-salt-acetone bath and a soln of acyl chloride
(2.2 mmol) in dry CH2Cl2 (10 mL) was added dropwise within
40 min. The reaction mixture was slowly warmed to rt and stirred
for a further 2 h, at the end of which time TLC (3:1 petroleum
ether–EtOAc) indicated the completion of the reaction. Water
(20 mL) was added to the reaction mixture. The aq soln was ex-
tracted with CH2Cl2 (3 ꢂ 20 mL), the extract was washed with M
HCl and satd aq sodium hydrogencarbonate, dried (Na2SO4), and
concentrated. The residue was subjected to silica-gel column chro-
matography (3:1–6:1 petroleum ether–EtOAc) to give the desired
products 6a–f and 7a–d in high yields.
1.9. 4-Methoxyphenyl 2,4-di-O-benzoyl–L-rhamnopyranosyl-
(1?2)-3,4-di-O-benzoyl-6-deoxy– -talopyranoside (11)
L
To a soln of 10 (1.28 g, 1.4 mmol) and Et3 N (0.38 mL, 2.8 mmol)
in THF (15 mL) was added PPh3 (110 mg, 0.42 mmol) and
Pd[P(C6H5)3]4 (81 mg, 0.07 mmol), and the mixture was stirred at
25 °C until TLC (3:1 petroleum ether–EtOAc) indicated completion
of the reaction. The reaction mixture was concentrated under
diminished pressure, and the residue was purified by flash chroma-
tography on a silica-gel column (4:1 petroleum ether–EtOAc) to
give 11 (0.94 g, 81%) as a white solid; ½a D25
ꢀ32.0 (c 0.5 CHCl3);
ꢁ
Analytical data for compounds 6a–f and 7a–d are enclosed in
Supplementary data.
1H NMR (300 MHz, CDCl3); d 1.31 (d, J 4.3 Hz, 3H, CH3), 1.33 (d, J
4.6 Hz, 3H, CH3), 2.07 (d, J 6.6 Hz, 1H, OH, exchangeable with
D2O), 3.80 (s, 3H, OCH3), 4.28–4.33 (m, 2H), 4.49–4.51 (m, 2H),
5.19 (s, 1H, H-1), 5.26–5.35 (m, 2H), 5.69 (s, 1H, H-1), 5.70 (m,
1H), 5.82 (dd, J2,3 = J3,4 = 3.6 Hz, 1H, H-3), 6.88–6.91 (m, 2H, Ar-
H), 7.08–7.11 (m, 2H, Ar-H), 7.35–7.64 (m, 12 H, Bz-H), 7.98–8.20
(m, 8H, Bz-H). Anal. Calcd for C47H44O14: C, 67.78; H, 5.33. Found:
C, 67.70; H, 5.60.
1.7. 3-O-Allyloxycarbonyl-2,4-di-O-benzoyl-a-L-
rhamnopyranosyl trichloroacetimidate (9)
To a soln of 4-methoxyphenyl 3-O-allyloxycarbonyl-2,4-di-O-
benzoyl-
-rhamnopyranoside (8)21 (8.43 g, 0.015 mol) in 80%
a-L
MeCN (400 mL) at 35 °C was added CAN (34.1 g, 0.06 mol). The
mixture was stirred at 35 °C for 0.5 h while TLC (4:1 petroleum
ether–EtOAc) indicated the completion of the reaction. The solvent
was evaporated under diminished pressure at 50 °C to give a resi-
due, which was dissolved in CH2Cl2, and washed with water. The
organic phase was dried (Na2SO4), concentrated, and then purified
by silica-gel column chromatography with 3:1 petroleum ether–
EtOAc as the eluent to give 3-O-allyloxycarbonyl-2,4-di-O-ben-
1.10. 4-Methoxyphenyl 2,3,4-tri-O-benzoyl–L-
rhamnopyranosyl-(1?3)-2,4-di-O-benzoyl–
L
-
-
rhamnopyranosyl-(1?3)-2,4-di-O-benzoyl–
L
rhamnopyranosyl-(1?2)-3,4-di-O-benzoyl-6-
deoxy– -talopyranoside (13)
L
To a cooled soln (ꢀ10 °C) of 11 (400 mg, 0.48 mmol) and 1222
zoyl-a-L
-rhamnopyranose (5.34 g, 78%) as a yellow foam. A mix-
(500 mg, 0.53 mmol) in anhyd CH2Cl2 (25 mL) was added TMSOTf
ture of this compound (5.34 g, 11.7 mmol), trichloroacetonitrile
(25
lL, 0.14 mmol). The mixture was stirred at this temperature
(4.0 mL, 40 mmol), and 1,8-diazabicyclo[5.4.0] undecene (DBU)
for 2 h, and then quenched with Et3N (2 drops). The solvent was

S. Yan et al. / Carbohydrate Research 343 (2008) 3107–3111
3111
evaporated under diminished pressure to give a residue, which was
purified by silica-gel column chromatography (3:1 petroleum
ether–EtOAc) to give the tetrasaccharide 13 (600 mg, 76%) as a foa-
Ministry (No.: 21168020) and the Doctoral Program Foundation
of Institutions of Higher Education of China (No.: 20070019072).
my solid; ½a 2D5
ꢁ
+78 (c 1.0 CHCl3); 1H NMR (600 MHz, CDCl3): d 0.79
Supplementary data
(d, J 6.6 Hz, 3H, CH3), 0.80 (d, J 6.6 Hz, 3H, CH3), 1.31 (d, J 6.6 Hz, 3H,
CH3), 1.34 (d, J 6.3 Hz, 3H, CH3), 3.74–3.76 (m, 1H, H-50), 3.79 (s, 3H,
OCH3), 3.81 (m, 1H, H-500), 4.18 (dd, J2,3 3.0 Hz, J3,4 9.6 Hz, 1H, H-30),
4.29 (dd, J1,2 1.2 Hz, J2,3 3.6 Hz, 1H, H-2), 4.30–4.33 (m, 1H, H-5000),
4.38 (dd, J2,3 3.0 Hz, J3,4 9.6 Hz, 1H, H-300), 4.48 (q, 1H, H-5), 4.69 (d,
J1,2 0.6 Hz, 1H, H-10), 4.84 (d, J1,2 1.2 Hz, 1H, H-1000), 5.13 (dd, J1,2 0.6,
J2,3 3.0 Hz, 1H, H-20), 5.17 (dd, J1,2 1.2 Hz, J2,3 3.0 Hz, 1H, H-2000), 5.29
(d, J1,2 1.8 Hz, 1H, H-100), 5.30 (dd, J3,4 = J4,5 = 9.6 Hz, 1H, H-40), 5.35
(dd, J3,4 = J4,5 = 9.6 Hz, 1H, H-4000), 5.46 (dd, J2,3 3.0 Hz, J3,4 9.6 Hz,
1H, H-3000), 5.50 (dd, J1,2 1.8 Hz, J2,3 3.0 Hz, 1H, H-200), 5.55 (dd,
J3,4 = J4,5 = 9.6 Hz, 1H, H-400), 5.66 (d, J3,4 3.6 Hz, 1H, H-4), 5.75 (d,
J1,2 1.2 Hz, 1H, H-1), 5.83 (dd, J2,3 = J3,4 = 3.6 Hz, 1H, H-3), 6.86–
7.24 (m, 7H), 7.27–7.75 (m, 32H), 8.10–8.14 (m, 10H); 13C NMR
(300 MHz, CDCl3); d 16.4, 16.9, 17.3, 17.8, 98.6 (C-1), 99.0 (C-1),
99.0 (C-1), 99.8 (C-1), 164.7, 165.4, 165.5, 165.5, 165.5, 165.7,
166.1, 166.3, 167.1 (9 BzCO). Anal. Calcd for C94H84O27: C, 68.61;
H, 5.14. Found: C, 68.89; H, 5.30.
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.carres.2008.09.010.
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1.11. 4-Methoxyphenyl
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deoxy– -talopyranoside (II)
L-rhamnopyranosyl-(1?3)–
L-
L
-rhamnopyranosyl-(1?2)-6-
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Tetrasaccharide 13 (200 mg, 0.12 mmol) was dissolved in satd
NH3–MeOH (30 mL). After 96 h at rt, the reaction mixture was con-
centrated, and the residue was purified by chromatography on
Sephadex LH-20 (MeOH) to afford II (77 mg, 91%) as a foamy solid;
½
a 2D5 +55.8 (c 0.5 H2O); 1H NMR (300 MHz, D2O): d 1.09–1.40 (m,
ꢁ
12H), 3.23–3.49 (m, 4H), 3.66–3.81 (m, 12H), 3.96–4.09 (m, 7H),
4.93 (s, 3H, 3 H-1), 5.41 (s, 1H, H-1), 6.84–6.97 (m, 4H, Ar-H); 13C
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98.9, 102.2, 102.5, 102.6 (4 C-1); MALDI-TOFMS: m/z 731.5
[M+Na+]; HRESIMS: calcd for [C31H48O18]Na+: 731.2735, found:
m/z 731.2733.
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This work was supported by the Scientific Research Foundation
for the Returned Overseas Chinese Scholars, State Education